The long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) has been demonstrated to participate in the deterioration of many types of cancer. However, the underlying mechanisms of SNHG1-mediating functions in osteosarcoma (OS) have yet to be elucidated. In the present study, our results showed that SNHG1 was upregulated in OS tissues and cell lines, and high SNHG1 expression predicts poor overall survival of OS patients. Knockdown of SNHG1 inhibited cell growth and metastasis of OS in vitro and in vivo. Furthermore, our data demonstrated that there was reciprocal repression between SNHG1 and miR-326 which act as a tumor suppressor in OS cells, and exhibiting a strong negative relationship between SNHG1 and miR-326 expression in OS tissues. Additionally, we identified that SNHG1 increased human nin one binding protein (NOB1), an oncogene, through sponging miR-326 as competing endogenous RNA (ceRNA), finally prompting cell growth, migration and invasion in OS. Collectively, these findings not only uncovered that the SNHG1/miR-326/NOB1 signaling axis has a key role in OS progression but also suggested the potential application of SNHG1 and miR-326 as biomarkers in the OS diagnosis and treatment.